Contributed by Rosemary Recavarren A, MD, Lydia Contis, MD and Jie Hu, PhD Published on line in November 2005

CLINICAL HISTORY:

A 61-year-old female with a past medical history of chronic lymphocytic leukemia (CLL) for 10 years, presented to the emergency room (ER) with left upper quadrant pain and multiple ecchymoses.
Her past medical history included treatment with Fludarabine (last dose more than one year ago), Rituximab and Cytoxan. Of note, she presented to the ER with a seizure 6 months previously. Studies revealed a left fronto-temporal lesion, which was resected and diagnosed as a meningioma. To prevent seizures, she was started on Dilantin. At a follow up visit in neurosurgery, CBC values indicated pancytopenia. Because this was thought to be related to Dilantin treatment, it was suspended and Levetiracetam was initiated, but there were no improvements in her counts.

A CT scan of the abdomen and pelvis in the current admission showed diffuse lymphadenopathy worrisome for lymphoma, and a splenic infarct in an enlarged spleen.

At the time of the biopsy the patient presented with a peripheral blood white count of 8.4 x 109/L with 19% atypical lymphoid cells, hemoglobin of 9.8g/dL, platelet count of 39 x 109/L.

HISTOLOGIC FINDINGS:

The peripheral blood (Fig. 1) and bone marrow aspirate (Fig. 2) show numerous very large atypical cells with a high nuclear/cytoplasmic ratio, irregular nuclear contours and prominent nucleoli (see arrow).

BONE MARROW BIOPSY, HEMATOXYLIN AND EOSIN STAIN:

The bone marrow biopsy (Fig. 3 and 4) is hypercellular (70%) and shows diffuse infiltration by large atypical cells with abundant cytoplasm, nuclei with open chromatin and many with prominent central nucleoli. Admixed are some small lymphocytes.

IMMUNOHISTOCHEMICAL STAINS IN BONE MARROW:

The infiltrate in the bone marrow is CD20 (Fig. 5) positive, CD5 positive (Fig. 6), with few scattered CD3 positive (Fig. 7) small lymphoid cells, and Ki-67 (Fig. 8) shows a high proliferation index. Cyclin-D1 was negative. In situ hybridization study for EBER was negative

FLOW CYTOMETRY IN BONE MARROW:

Flow cytometric immunophenotypic studies show a population of large cells (see arrow). This population coexpresses CD5 and CD19, is dim CD20 positive, CD22 positive, CD10 negative, FMC7 negative, ZAP-70 positive, and CD38 positive.